MCID: 3MT013
MIFTS: 38

3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome

Categories: Genetic diseases, Rare diseases, Liver diseases, Ear diseases, Neuronal diseases, Metabolic diseases, Fetal diseases

Aliases & Classifications for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

MalaCards integrated aliases for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

Name: 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome 53 12 24 71 28 13 14 69
Megdel Syndrome 12 23 49 24 55
Serac1 Defect 23 49 24
Megdel 53 12 71
Mgca6 53 12 71
3-Methylglutaconic Aciduria, Type Vi 53 71
Megdhel Syndrome 23 24
3-Methylglutaconic Aciduria with Dystonia-Deafness, Hepatopathy, Encephalopathy, and Leigh-Like Syndrome; Megdhel 53
3-Methylglutaconic Aciduria with Dystonia-Deafness, Hepatopathy, Encephalopathy, and Leigh-Like Syndrome 53
3-Methylglutaconic Aciduria Type Iv with Sensorineural Deafness, Encephalopathy, and Leigh-Like Syndrome 24
3-Methylglutaconic Aciduria Type Iv with Sensorineural Deafness, Encephalopathy and Leigh-Like Syndrome 69
3-Methylglutaconic Aciduria with Deafness, Encephalopathy,leigh-Like Syndrome 23
3-Methylglutaconic Aciduria with Deafness-Encephalopathy-Leigh-Like Syndrome 55
3-Methylglutaconic Aciduria, Type Vi; Mgca6 53
3-Methylglutaconic Aciduria Type Vi 49
3-Methylglutaconic Aciduria Type 6 12
Megdhel 53

Characteristics:

Orphanet epidemiological data:

55
megdel syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or early childhood


HPO:

31
3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

OMIM : 53 MEGDEL is an autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome (256000). Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells (summary by Wortmann et al., 2012). About 50% of patients develop severe, but transient, liver dysfunction and/or signs of liver failure, in the neonatal period or during the first year of life, prompting some authors to suggest the name 'MEGDHEL' syndrome, with the 'H' referring to 'hepatopathy' (summary by Maas et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950). (614739)

MalaCards based summary : 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome, also known as megdel syndrome, is related to 3-methylglutaconic aciduria and 3-methylglutaconic aciduria, type iv, and has symptoms including seizures, abnormality of extrapyramidal motor function and dystonia. An important gene associated with 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome is SERAC1 (Serine Active Site Containing 1). Affiliated tissues include brain and liver.

Disease Ontology : 12 A 3-methylglutaconic aciduria that has material basis in homozygous or compound heterozygous mutation in the SERAC1 gene on chromosome 6q25.

Genetics Home Reference : 24 MEGDEL syndrome is an inherited disorder that affects multiple body systems. It is named for several of its features: 3-methylglutaconic aciduria (MEG), deafness (D), encephalopathy (E), and Leigh-like disease (L).

UniProtKB/Swiss-Prot : 71 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome: An autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome. Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells.

GeneReviews: NBK195853

Related Diseases for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Diseases related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 3-methylglutaconic aciduria 27.7 AUH DNAJC19 OPA3 SERAC1 TMEM70
2 3-methylglutaconic aciduria, type iv 27.5 AUH DNAJC19 OPA3 SERAC1 TMEM70
3 branchiootic syndrome 1 10.1
4 encephalopathy 10.1
5 leigh syndrome 9.8
6 microcephaly 9.8
7 epilepsy 9.8
8 dystonia 9.8
9 not otherwise specified 3-mga-uria type 9.8
10 organic acidemia 9.6 SERAC1 TMEM70
11 3-methylglutaconic aciduria, type i 8.7 AUH DNAJC19 OPA3 TMEM70
12 3-methylglutaconic aciduria, type v 8.5 AUH DNAJC19 OPA3 SERAC1 TMEM70
13 3-methylglutaconic aciduria, type iii 8.4 AUH DNAJC19 OPA3 SERAC1 TMEM70

Graphical network of the top 20 diseases related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:



Diseases related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
dystonia
brain atrophy
spasticity
cerebellar atrophy
mental retardation
more
Metabolic Features:
hypoglycemia
lactic acidosis

Immunology:
recurrent infections
neonatal sepsis

Head And Neck Ears:
hearing loss, sensorineural

Head And Neck Head:
microcephaly (1 patient)

Growth Other:
failure to thrive

Laboratory Abnormalities:
increased serum lactate
hyperammonemia
3-methylglutaconic aciduria
defects in mitochondrial oxidative phosphorylation
abnormal phospholipid profile
more
Muscle Soft Tissue:
hypotonia
degrading mitochondria

Abdomen Gastroin testinal:
feeding problems


Clinical features from OMIM:

614739

Human phenotypes related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

31 (show all 23)
# Description HPO Frequency HPO Source Accession
1 seizures 31 occasional (7.5%) HP:0001250
2 abnormality of extrapyramidal motor function 31 HP:0002071
3 dystonia 31 HP:0001332
4 brain atrophy 31 HP:0012444
5 intellectual disability 31 HP:0001249
6 spasticity 31 HP:0001257
7 failure to thrive 31 HP:0001508
8 developmental regression 31 HP:0002376
9 global developmental delay 31 HP:0001263
10 microcephaly 31 occasional (7.5%) HP:0000252
11 sensorineural hearing impairment 31 HP:0000407
12 hypoglycemia 31 HP:0001943
13 feeding difficulties 31 HP:0011968
14 increased serum lactate 31 HP:0002151
15 lactic acidosis 31 HP:0003128
16 recurrent infections 31 HP:0002719
17 hyperammonemia 31 HP:0001987
18 cerebellar atrophy 31 HP:0001272
19 encephalopathy 31 HP:0001298
20 generalized hypotonia 31 HP:0001290
21 abnormality of the coagulation cascade 31 HP:0003256
22 neonatal sepsis 31 HP:0040187
23 3-methylglutaconic aciduria 31 HP:0003535

UMLS symptoms related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:


muscle spasticity, abnormality of extrapyramidal motor function

Drugs & Therapeutics for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Search Clinical Trials , NIH Clinical Center for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome

Genetic Tests for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Genetic tests related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

# Genetic test Affiliating Genes
1 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome 28 SERAC1

Anatomical Context for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

MalaCards organs/tissues related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

38
Brain, Liver

Publications for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Articles related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

# Title Authors Year
1
Transient neonatal renal failure and massive polyuria in MEGDEL syndrome. ( 27331002 )
2016
2
Diagnosis and Management of Drooling in Children With Progressive Dystonia: A Case Series of Patients With MEGDEL Syndrome. ( 27229007 )
2016
3
Two Turkish siblings with MEGDEL syndrome due to novel SERAC1 gene mutation. ( 27186703 )
2015
4
In-silico modelling of SERAC1: Protein involved in a developmental neural disorder MEGDEL syndrome characterized by 3-methyl glutaconic aciduria type IV with sensory-neural deafness, encephalopathy and Leigh-like syndrome. ( 26531334 )
2015
5
MEGDEL Syndrome in a Child From Palestine: Report of a Novel Mutation in SERAC1 Gene. ( 25051967 )
2014
6
Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1. ( 23918762 )
2013
7
Mutations in the phospholipid remodeling gene SERAC1 cause MEGDEL syndrome. ( 23401890 )
2012
8
MEGDEL Syndrome ( 24741715 )
1993

Variations for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

UniProtKB/Swiss-Prot genetic disease variations for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

71
# Symbol AA change Variation ID SNP ID
1 SERAC1 p.Gly401Asp VAR_068442
2 SERAC1 p.Gly404Glu VAR_068443
3 SERAC1 p.Ser498Thr VAR_068445 rs201941476

ClinVar genetic disease variations for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SERAC1 NM_032861.3(SERAC1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs387907236 GRCh38 Chromosome 6, 158146827: 158146827
2 SERAC1 NM_032861.3(SERAC1): c.1167_1170delTCAG (p.Gln390Profs) deletion Pathogenic rs772296795 GRCh37 Chromosome 6, 158540199: 158540202
3 SERAC1 NM_032861.3(SERAC1): c.1435_1437delCTT (p.Leu479del) deletion Pathogenic GRCh37 Chromosome 6, 158537281: 158537283
4 SERAC1 NM_032861.3(SERAC1): c.202C> T (p.Arg68Ter) single nucleotide variant Pathogenic rs529232938 GRCh37 Chromosome 6, 158571548: 158571548
5 SERAC1 NM_032861.3(SERAC1): c.265_265+1insCATG insertion Likely pathogenic rs797045105 GRCh37 Chromosome 6, 158571484: 158571485
6 SERAC1 NM_032861.3(SERAC1): c.1628_1629dupCT (p.Val544Leufs) duplication Pathogenic rs767780913 GRCh37 Chromosome 6, 158535876: 158535877
7 SERAC1 NM_032861.3(SERAC1): c.1643_1646dup (p.Leu550Serfs) duplication Pathogenic rs761964407 GRCh37 Chromosome 6, 158535859: 158535862
8 SERAC1 NM_032861.3(SERAC1): c.1403+1G> C single nucleotide variant Pathogenic rs1131690799 GRCh38 Chromosome 6, 158117726: 158117726
9 SERAC1 NM_032861.3(SERAC1): c.1577G> A (p.Gly526Glu) single nucleotide variant Pathogenic GRCh38 Chromosome 6, 158114896: 158114896

Expression for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Search GEO for disease gene expression data for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome.

Pathways for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

GO Terms for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

Cellular components related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.02 AUH DNAJC19 OPA3 SERAC1 TMEM70

Biological processes related to 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-Like Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 visual perception GO:0007601 8.62 DNAJC19 OPA3

Sources for 3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and...

3 CDC
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9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
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29 HGMD
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32 ICD10
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65 SNOMED-CT via HPO
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